Cancer Cell Biology

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Evidence for a pathophysiological role of cysteinyl leukotrienes in classical Hodgkin lymphoma

  1. Frida Schain1,†,*,
  2. Ylva Tryselius2,‡,
  3. Jan Sjöberg1,‡,
  4. Anna Porwit3,
  5. Linda Backman2,
  6. Maria Malec1,3,
  7. Dawei Xu1,
  8. Martina Vockerodt4,
  9. Karl R.N. Baumforth4,
  10. Wenbin Wei4,
  11. Paul G. Murray4,
  12. Magnus Björkholm1,
  13. Hans-Erik Claesson1,2,5

Article first published online: 14 AUG 2008

DOI: 10.1002/ijc.23781

Issue

International Journal of Cancer

International Journal of Cancer

Volume 123, Issue 10, pages 2285–2293, 15 November 2008

Additional Information

How to Cite

Schain, F., Tryselius, Y., Sjöberg, J., Porwit, A., Backman, L., Malec, M., Xu, D., Vockerodt, M., Baumforth, K. R., Wei, W., Murray, P. G., Björkholm, M. and Claesson, H.-E. (2008), Evidence for a pathophysiological role of cysteinyl leukotrienes in classical Hodgkin lymphoma. International Journal of Cancer, 123: 2285–2293. doi: 10.1002/ijc.23781

Author Information

  1. 1

    Department of Medicine, Division of Hematology, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden

  2. 2

    Orexo AB, Berzelius väg 3, Solna, Sweden

  3. 3

    Department of Pathology, Karolinska University Hospital Solna, Stockholm, Sweden

  4. 4

    CRUK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, United Kingdom

  5. 5

    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

  1. †

    Fax: +46-8-51773054

  2. ‡

    Ylva Tryselius and Jan Sjöberg contributed equally to this work.

*Centre for Molecular Medicine, Division of Hematology, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden

Publication History

  1. Issue published online: 12 SEP 2008
  2. Article first published online: 14 AUG 2008
  3. Manuscript Accepted: 28 MAY 2008
  4. Manuscript Received: 20 NOV 2007

Funded by

  • Swedish Cancer Society
  • Stockholm County Council
  • Karolinska Institutet
  • Biolipox AB
  • Orexo AB
  • Leukaemia Research Fund, UK

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Keywords:

  • leukotrienes;
  • cysteinyl leukotriene receptors;
  • Hodgkin lymphoma;
  • cytokines;
  • chemokines

Abstract

Classical Hodgkin lymphoma (cHL) is characterized histologically by a minority of malignant Hodgkin Reed-Sternberg cells surrounded by abundant inflammatory cells, generally believed to be of major importance in the pathophysiology of the disease. Here, we present data that link inflammatory cell-derived arachidonic acid metabolites, the cysteinyl leukotrienes (CysLT), to the pathogenesis of cHL. Two HL cell lines, L1236 and KMH2, were shown to express functional CysLT1 receptors, responding with a robust calcium signal upon leukotriene (LT) D4 challenge. LTD4 stimulated protein release of tumor necrosis factor-α, interleukin-6 and -8 by L1236 cells and interleukin-8 by KMH2 cells. Importantly, all these LTD4-induced effects were blocked by the CysLT1 receptor-specific antagonist zafirlukast. Immunohistochemical studies of cHL biopsies and microarray analysis of microdissected cells revealed that the CysLT1 receptor is expressed also by primary Hodgkin Reed-Sternberg cells. As these cells are surrounded by CysLT-producing eosinophils, macrophages and mast cells, our results suggest the CysLTs as mediators in the pathogenesis of cHL, contributing to the aberrant cytokine network of this lymphoma. © 2008 Wiley-Liss, Inc.

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